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与哮喘潜在相关的ADAM33分子相互作用网络及通路研究

Molecular interaction network and pathway studies of ADAM33 potentially relevant to asthma.

作者信息

Vishweswaraiah Sangeetha, Veerappa Avinash M, Mahesh Padukudru A, Jayaraju Biligere Siddaiah, Krishnarao Chaya Sindaghatta, Ramachandra Nallur B

机构信息

Genetics and Genomics Laboratory, Department of Studies in Zoology, University of Mysore, Mysore, Karnataka, India.

Department of Pulmonology, JSS Hospital, Mysore, Karnataka, India.

出版信息

Ann Allergy Asthma Immunol. 2014 Oct;113(4):418-24.e1. doi: 10.1016/j.anai.2014.07.009. Epub 2014 Aug 22.

Abstract

BACKGROUND

Asthma is a complex disease caused by gene-gene, gene-protein, and protein-protein interactions and the influence of environment, which plays a significant role in causing asthma pathogenesis. ADAM33 is known to be an important gene involved in asthma pathogenesis. No one single gene is a causal factor of asthma; rather, asthma is caused by a complex interaction of multiple genes having pathogenetic and protective effects.

OBJECTIVE

To identify and understand the interacting genes and proteins of ADAM33.

METHODS

The Ingenuity Pathway Analysis and GeneMANIA tools and a literature survey were used to identify the interacting candidates of ADAM33 and the WEB-based GEne SeT AnaLysis Toolkit was used to perform enrichment analysis of the proteins identified.

RESULTS

Keeping ADAM33 as a major hub, the authors identified some proteins whose interaction with ADAM33 had been associated with asthma and they recognized some proteins, such as amyloid β (A4) precursor protein, ataxin-7, α4-integrin, α5-integrin, α9-integrin, tissue inhibitor of metalloproteinase-4, and ubiquilin-4, that had not been previously associated with asthma.

CONCLUSION

The proteins identified in this study were enriched for various mechanisms that are involved in airway hyperresponsiveness, and through the interaction with ADAM33, they may have potential relevance in asthma.

摘要

背景

哮喘是一种由基因-基因、基因-蛋白质和蛋白质-蛋白质相互作用以及环境影响所导致的复杂疾病,在哮喘发病机制中起重要作用。已知ADAM33是参与哮喘发病机制的一个重要基因。没有单一基因是哮喘的致病因素;相反,哮喘是由具有致病和保护作用的多个基因的复杂相互作用引起的。

目的

识别并了解ADAM33的相互作用基因和蛋白质。

方法

使用Ingenuity Pathway Analysis和GeneMANIA工具以及文献调查来识别ADAM33的相互作用候选基因,并使用基于网络的基因集分析工具包对所识别的蛋白质进行富集分析。

结果

以ADAM33作为主要枢纽,作者识别出了一些与ADAM33相互作用且与哮喘相关的蛋白质,还识别出了一些此前未与哮喘相关联的蛋白质,如淀粉样β(A4)前体蛋白、共济失调蛋白7、α4整合素、α5整合素、α9整合素、金属蛋白酶组织抑制剂4和泛素连接蛋白4。

结论

本研究中识别出的蛋白质在涉及气道高反应性的各种机制中富集,并且通过与ADAM33相互作用,它们可能与哮喘存在潜在关联。

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